Production of an acid of the ascorbic acid type from a 2-keto-hexonic acid



Patented Mar. 25, 1952 PRODUCTION OF AN ACID OF THE ASCORBIC ACID TYPE FROM A Z-KETO-HEXONIC ACID Viktor Ettel, Prague, Czechoslovakia, assignor to Spclek pro chemickou a hutni vyrobu, narodni podnik, also named United Chemical and Metallurgical Works, National Corporation, Prague, Czechoslovakia N Drawing. Application May 10, 1949, Serial No. 92,520. In Czechoslovakia May 13, 1948 3 Claims. 1 It is known that 2-keto-hexonic acids, if necessary their-esters, can be transformed in alkaline or acid media into corresponding acids of the ascorbic acid type of the composition as follows:

00 00 not? H0('; 7 I] l! 0 H00 H00 l H n Ho in OH bmon JHiOH The reaction, by which ascorbic acid is formed from the 2-keto-hexonic acids, occurs by enolisa- The subject of this invention is a method for I the enolisation of 2-keto-hexonic acids in alkaline medium in the presence; of amphoteric hydroxides of heavy metals, which form compounds with alkalies, as for example, Pb(OH)2 or Zn(OH)2, in water-free solvents. The amphoteric heavy metals are used in the form of their alkali compounds of the type Me(ONa)OH (Me=amphoteric metal) in a suspension or solution of water-free solvents. In this way the enolisation takes place very rapidly with heating, namely in the course of few minutes, and with good yield. At the same time the ascorbic acid is deposited in the form of diificultly soluble salts of the amphoteric metals, by which means the isolation of this acid in pure state from the reaction mixture is made possible in suitable manner. The method according to the invention is especially suited for the enolisation of difiicultly crystallizing esters" of the Z-ketohexonic acids, from which completely pure ascorbic acids are then obtained. Pbor Zn-salts of the ascorbic acid are disintegrated by the action of H2SO4 or H28 in an organic solvent. The yield in pure substance is 70-80% of the theory. The reaction generally proceeds according to the following scheme:

tion. This represents substantially the rearrangement of an H-atom on to the neighbouring CO-- group, a double bond according to the scheme I being formed between the relevant C-atoms (the remaining H-atom can be represented by another group, in this case by the OI-I-- group).

As is well known the 2-keto-hexonic acids, if necessary their esters, can be transformed into corresponding ascorbic acids by enolisation in alkaline or acid media. In the enolisation with acids furol and other disintegrating products are produced, which decrease the yield of ascorbic acid and render its isolation difficult. On the other hand the enolisation of methyl esters with alkalis in water-free solvents aiiords much better results, the reaction taking place in shorter time with good yie1d.

about 20% of the theory.

Examples of carrying out the'process 1. 10 parts of methyl ester of the2-ket0-lidonic acid (gulonic acid) are dissolved in 100 parts of water-free methanol and enolized with a suspension 01'' 6 parts of sodium zincate Zn(ONa)OI-I in 50 parts of water-free methanol for ten minutes at a temperature of C. in reflux condensation. By the reaction zinc-l ascorbinate is formed in a yield of' 8i0 to of the theory. Complete precipitation of the zinc salt is obtained by the cooling of the reaction mixture and addition of 50 parts of ether. The slightly yellow coloured deposit of zinc-l-ascorbinate is suctioned ofi, suspended moist in 100 parts of water-free methanol and precipitated with an equivalent amount of H2804. or H23.

The separated ZnSO4 or ZnS is filtered off and the filtrate concentrated in vacuo at 20 C. 6.2 to 6.5 parts of l-ascorbic acid is obtained, that is a yield of 74 to 77% of the theory. The product recrystallized from methanol has a melting point of 181 to 185 C.

2. parts of methyl ester of the 2-keto-dgluconic acid are dissolved in 200 parts of waterfree methanol, enolized with a suspension of Zn(ONa)OH and treated further according to Example 1. The yield of the isoascorbic acid formed amounts to 75 to 78% of the theory. The pure product recrystallized from methanol melts at 173 C.

3. 10 parts of methyl ester of the 2-keto-lidonic acid are dissolved in 100 parts of waterfree methanol and enolized with a suspension of 13 parts of Pb(ONa) OH in 50 parts of waterfree methanol for 15 to minutes at a temperature of 65 C. in reflux condensation. l-ascorbic acid with a yield of 70% of the theory is produced by the enolization, as was established by titration. The separated yellow lead salt is filtered ofi after the cooling of the reaction mixture, suspended still moist in water-free methanol and precipitated with HzS or by addition of an equivalent amount of H2804. The separated PbS or PbSO4, is filtered and the filtrate containing l-ascorbic acid concentrated in vacuo. The yield of pure substance amounts to 60 to 65% of the theory and its melting point is 180 to hexonic acid by heating them in a water-free lower alcohol with an alkali compound of amphoteric hydroxides of heavy metals selected from the group Pb and Zn treating this precipitate of a metal salt of ascorbic acid with a substance selected from the group consisting of hydrogen sulphide and sulphuric acid, filtering to obtain a filtrate containing soluble ascorbic acid, concentrating the filtrate, and Working up the concentrate to pure ascorbic acid.

2. A process for the production of an acid of the ascorbic acid type from a 2-keto-hexonic acid, which comprises enolizing esters of Z-ketohexonic acid by heating them in a water-free lower alcohol with an alkali compound of amphoteric hydroxides of heavy metals selected from the group Pb and Zn, treating this precipitate of a metal salt of ascorbic acid with a substance selected from the group consisting of hydrogen sulphide and sulphuric acid, filtering to obtain a filtrate containing soluble ascorbic acid, concentrating the filtrate, and working up the concentrate to pure ascorbic acid.

3. A process for the production of an acid of the ascorbic acid type from a 2-keto-hexonic acid, which comprises enolizing esters of 2-ketohexonic acid by heating them in a water-free lower alcohol with an alkali compound of amphoteric hydroxides of heavy metals selected from the group Pb and Zn to precipitate a heavy metal salt of ascorbic acid, treating this precipitate with a substance selected from the group consisting of hydrogen sulphide and sulphuric acid, filtering to obtain a filtrate containing soluble ascorbic acid, concentrating the filtrate in vacuo at a low temperature, and working up the concentrate to pure ascorbic acid.

VIKTOR ETTEL.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,265,121 Reichstein Dec. 2, 1941 2,443,487 Wenner June 15, 1948 FOREIGN PATENTS Number Country Date 469,157 Great Britain July 20, 1937 

1. A PROCESS FOR THE PRODUCTION OF AN ACID OF THE ASCORBIC ACID TYPE FROM A 2-KETO-HEXONIC ACID, WHICH COMPRISES ENOLIZING ESTERS OF 2-KETOHEXONIC ACID BY HEATING THEM IN A WATER-FREE LOWER ALCOHOL WITH AN ALKALI COMPOUND OF AMPHOTERIC HYDROXIDES OF HEAVY METALS SELECTED FROM THE GROUP PB AND ZN TREATING THIS PRECIPITATE OF A METAL SALT OF ASCORBIC ACID WITH A SUBSTANCE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN SULPHIDE AND SULPHIDE ACID, FILTERING TO OBTAIN A FILTRATE CONTAINING SOLUBLE ASCORBIC ACID, CONCENTRATING THE FILTRATE, AND WORKING UP THE CON CENTRATE TO PURE ASCORBIC ACID, 